Human immunodeficiency virus type 1 and 2 (HIV-1 and HIV-2) are known to cause acquired immune deficiency syndrome (AIDS). Both viruses apparently exhibit similar modes of transmission. HIV-1 and HIV-2 were both isolated in the early 1980's from African AIDS patients. Since then, cases have been found in most countries of the world. Because the HIV viruses exhibit rapid genetic drift, widely divergent strains are emerging. Detection and treatment of variant strains has proven to be challenging and difficult.
Individuals with antibodies reactive with HIV-1 and/or HIV-2 are determined by immunoassays of the conventional sandwich ELISA format. These assays are comprised of an immobilized viral antigen, that may be comprised of viral lysate, retrovirus proteins or natural or synthetic polypeptides, that is contacted with blood or serum components suspected of containing HIV antibodies. While the existing commercial tests appear to have significantly diminished the transmission of HIV virus in blood products, each test configuration may have some disadvantages.
The possible disadvantages of viral lysate tests include: the need to grow and handle large quantities of live infectious virus; the possibility that the live virus might be incorporated into test materials; the variable nature of the resulting viral lysate; and the substantial number of false positive and false negative results that require additional confirmatory testing. These disadvantages may also be associated with the use of isolated viral proteins as antigens.
The use of synthetic polypeptides, which can be engineered to immunologically mimic antigenic epitopes of the HIV viruses, may avoid some of the above-mentioned disadvantages. One area of concern with the use of synthetic polypeptides (less than or equal to 60 residues in length) in diagnostic assays is the consideration that viral antigenic drift could result in the failure to detect HIV-1 or HIV-2 infected sera using these assays, presumably due to the limited presentation of viral epitopes. One method of guarding against such an occurrence is to include polypeptides from different immunodominant regions of the viral genome. Thus, synthetic polypeptides that immunologically mimic immunodominant regions of the HIV-1 and HIV-2 pol gene products are important additions to the already described polypeptides that mimic the env, gag, and pol proteins of HIV-1 and HIV-2. U.S. Pat. Nos. 4,629,783 and 5,075,211 describe synthetic polypeptides that mimic antigenic determinants of HIV-1. Cosand U.S. Pat. No. 5,075,211 describes synthetic polypeptides that immunologically mimic antigenic epitopes of HIV-1 proteins from the pol region, including two polypeptides which are similar to the polypeptides of this invention. In blood screening assays, the greater the immunoreactivity of the antigens used in the assay method, the less likely antibodies to a new variant or subtype of HIV-1 or HIV-2, present in a patient's sample, will be left undetected.
U.S. Pat. No. 5,306,466 describes an “HIV-3 retrovirus” which was initially believed to be separate and distinct from HIV-1 and HIV-2. Researchers have since determined that the HIV-3 retrovirus is merely a particular subtype of HIV-1, now referred to as subtype O, or Group O. [R. De Leys, et. al., J. Virol.: 1207–1216 (1990); L. G Gürtler, et. al., J. Virol.:1581–1585 (1994)]
By comparing various HIV-1 isolates researchers have shown that some regions of the genome are highly variable while others are reasonably well conserved. Similar polymorphisms have also been observed for HIV-2.
Despite the apparent similarities in disease state and transmission of HIV-1 and HIV-2 viruses, the virus types have been differentiated based on their genetic divergence. Based on genetic analysis viral isolates can be grouped according to their genetic homology to previous isolates. Today, HIV-1 and HIV-2 form the two main branches of the HIV genetic tree. DNA hybridization studies suggest that, while regions of extensive homology exist between HIV-1 and HIV-2, other regions seem very divergent. (Clavel et al, Science 233: 343 (1986)). In fact, HIV-2 has been shown to have overall, only about 40% homology with HIV-1, and studies have shown little immunological cross reactivity between the envelope glycoproteins. The limited serologic cross reactivity between these viruses makes screening assays based on HIV-1 antigens insufficient for screening or diagnosis of HIV-2 infection in human sera.